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Updated: Jun 1, 2026
Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies
Published on: June 9, 2013
Matrix metalloproteinase inhibition counteracts impairment of cortical experience-dependent plasticity after
A Cybulska-Klosowicz1, M Liguz-Lecznar, D Nowicka
1Department of Molecular and Cellular Neurobiology, Nencki Institute, 3 Pasteur Street, 02-093 Warsaw, Poland.
Abstract:
Matrix metalloproteinases (MMPs) are fine modulators of brain plasticity and pathophysiology. The inhibition of MMPs shortly after ischaemic stroke reduces the infarct size and has beneficial effects on post-stroke behavioural recovery. Our previous studies have shown that photothrombotic cortical stroke disrupts use-dependent plasticity in the neighbouring cortex. The aim of the present study was to check whether the inhibition of MMPs after photothrombosis rescued the plastic capacity of the barrel cortex. To induce plasticity in adult mice, a unilateral deprivation of all vibrissae except row C was applied. The deprivation started immediately after stroke and lasted 7 days. This procedure, in control (non-stroke) animals, results in an enlargement of functional representation of the spared row, as shown with [(14)C]2-deoxyglucose uptake mapping. In mice with stroke induced by photothrombosis in the vicinity of the barrel cortex, vibrissae deprivation did not result in an enlargement of the cortical representation of the spared row C of vibrissae, which confirmed our previous results. However, when mice were injected with the broad-spectrum inhibitor of MMPs FN-439 (10 mg/kg, i.v.) immediately before a stroke, an enlargement of the representation of the spared row similar to the enlargement found in sham mice was observed. These results indicate the involvement of MMPs in the impairment of use-dependent plasticity in the vicinity of an ischaemic lesion.
Insights
Inhibiting matrix metalloproteinases (MMPs) after a stroke helps restore brain plasticity. This study shows MMP inhibition rescues use-dependent plasticity in the barrel cortex following photothrombotic stroke.
Area of Science:
- Neuroscience
- Neuroplasticity
- Stroke Research
Background:
- Matrix metalloproteinases (MMPs) influence brain plasticity and stroke pathophysiology.
- MMP inhibition post-stroke can reduce infarct size and improve recovery.
- Previous research indicated photothrombotic stroke impairs use-dependent plasticity.
Purpose of the Study:
- To investigate if MMP inhibition can restore plastic capacity in the barrel cortex after photothrombotic stroke.
- To determine the role of MMPs in the disruption of use-dependent plasticity near ischemic lesions.
Main Methods:
- Adult mice underwent photothrombotic stroke near the barrel cortex.
- Unilateral vibrissae deprivation (row C spared) was used to induce plasticity.
- Mice received a broad-spectrum MMP inhibitor (FN-439) or vehicle.
- Functional cortical representation was mapped using [(14)C]2-deoxyglucose uptake.
Main Results:
- Vibrissae deprivation failed to induce plasticity in stroke-affected mice.
- MMP inhibition with FN-439 prior to stroke restored plasticity, evidenced by enlarged cortical representation of spared vibrissae.
- Control (non-stroke) animals showed expected plasticity changes.
Conclusions:
- Matrix metalloproteinases (MMPs) play a critical role in impairing use-dependent plasticity after ischemic lesions.
- Inhibiting MMPs presents a potential therapeutic strategy to preserve or restore brain plasticity post-stroke.
